Heated Tobacco Products and Chronic Obstructive Pulmonary Disease: A Narrative Review of Peer-Reviewed Publications - European Medical Journal

Heated Tobacco Products and Chronic Obstructive Pulmonary Disease: A Narrative Review of Peer-Reviewed Publications

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Wolfgang Popp,1 *Lindsay Reese,2 Elena Scotti2

Scotti and Reese are employees of Philip Morris International. Popp works as a self-employed pulmonologist in Vienna.


Philip Morris International is the sole source of funding and sponsor of this research.

EMJ. ;8[1]:59-68. DOI/10.33590/emj/10309781. https://doi.org/10.33590/emj/10309781.
Chronic obstructive pulmonary disease (COPD), harm reduction, heated tobacco products (HTP), respiratory diseases, smoking.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.


An estimated 65 million people worldwide have moderate or severe chronic obstructive pulmonary disease (COPD), an umbrella term used to describe a group of progressive lung diseases that obstruct airflow such as emphysema and chronic bronchitis. Smoking contributes to an estimated 90% of COPD cases, as the harmful chemicals produced during tobacco combustion damage the lungs and airways. Although smoking cessation is the only intervention shown to improve COPD prognosis in smokers, many patients who try to quit continue to smoke. The continued use of conventional cigarettes exacerbates COPD symptoms, and globally more than 3 million people die from the disease every year. The last two decades have seen the introduction of combustion-free nicotine delivery alternatives that produce significantly lower levels of the harmful components in cigarette smoke, and researchers have begun to assess the impact of switching from cigarettes to these products. Several studies have examined how patients with COPD use e-cigarettes as assistance for quitting, but few have examined how heated tobacco products (HTP) may reduce risk. This narrative review summarises results from pre-clinical, clinical, and real-world evidence studies showing possible harm reduction benefits for patients with COPD who switch to HTPs rather than continuing to smoke cigarettes. Epidemiological studies, real-world data analyses, and randomised clinical trials must be conducted to determine whether switching from cigarettes to HTPs can improve health outcomes in patients with COPD who would otherwise continue to smoke combustible cigarettes.


Chronic obstructive pulmonary disease (COPD) is a preventable lung condition that represents a major and growing cause of global morbidity and mortality, and is primarily due to cigarette smoking.1,2 The World Health Organization (WHO) cites it as the third leading cause of death after ischaemic heart disease and stroke.3 The mortality risk from COPD is 12–13 times greater in smokers of combustible cigarettes,4 and an estimated 80–90% of patients with COPD smoke(d).5 Beyond the 3 million deaths attributed to COPD annually, the condition also has a major impact on healthcare systems: all smoking-related diseases, including COPD, are responsible for 1.5–6.8% of national health system expenditures worldwide.6

COPD is not a singular respiratory disease; it encompasses a range of treatable (but not curable) chronic lung conditions (including chronic bronchitis and emphysema) characterised by respiratory symptoms, progressively worsening airflow limitation, and resultant airway inflammation. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines,7 lung function evaluation via spirometry testing (e.g., forced expiratory volume in one second [FEV1] and forced vital capacity) is the gold standard for diagnosing COPD and tracking disease progression. However, COPD is widely thought to be underdiagnosed, and many current smokers who do not meet the diagnostic standards do have respiratory symptoms without airflow obstruction.7

The symptoms of COPD are induced and exacerbated by exposure to cigarette smoke,8 which causes inflammation and oxidative stress.9 There is no question that smoking cessation is by far the best approach to reduce disease progression in patients of any age. Most subjects with COPD are or were smokers and therefore have first-hand experience with the detrimental effects of cigarettes, but multiple studies reported that roughly half of smokers with COPD attempted to quit smoking in the past year.10-12 Unfortunately, only approximately 20% of patients with COPD are successful for 1 year,13 and many eventually relapse. Considering this small percentage, complementary tobacco harm reduction approaches should also be considered for this specific population of adult smokers.

Chronic Obstructive Pulmonary Disease and Cigarette Smoke

The primary cause of smoking-related disease and mortality is the harmful and potentially harmful constituents (HPHC) formed during tobacco combustion. A burning cigarette releases a complex mixture of ultrafine solid and gaseous particles, and more than 6,000 chemical constituents, approximately 100 of which have been identified by public health authorities as HPHCs linked to smoking-related diseases. These include particulates, oxidising chemicals, polycyclic aromatic hydrocarbons, acrolein, butadiene, metals (e.g., cadmium), and carbon monoxide (CO). These HPHCs are deposited throughout the respiratory tract, leading to cilia toxicity, oxidative stress, inflammation, impairment of lung defences, and irritation.9 Their continued presence causes changes in airway and alveolar cells, and affects tissue functions. This adversely impacts overall pulmonary function, eventually leading to the development of COPD. The most common symptoms are dyspnoea, increased sputum or mucus production, and chronic cough.

Smoke-Free Products

Although the best way to reduce the risks of developing COPD and other smoking-related diseases is to quit tobacco altogether, many people still want to continue using products with similar taste, ritual, and nicotine uptake.14 Recent scientific and technological advances have facilitated the development of innovative smoke-free products (SFP) that have the potential to be less harmful than continued smoking and are acceptable to and may be used by current adult smokers. The most widely used SFPs are e-cigarettes and HTPs. The former vaporises an e-liquid solution when it is puffed, while the latter heats real tobacco. E-cigarettes and HTPs operate differently, but they share the absence of combustion while still providing a satisfactory sensory experience for adult smokers.15-17

HTPs are designed to generate a nicotine-containing aerosol by heating tobacco to temperatures sufficient to release nicotine and flavours from the tobacco (<350 °C), but low enough to prevent the tobacco from burning (400–800 °C in conventional cigarettes).18 As a result, HTP aerosol contains fewer and lower levels of HPHCs than cigarette smoke (Figure 1).19

Figure 1: Differences between cigarette smoke and heated tobacco product aerosol.
HTP: heated tobacco product.
Adapted from PMIscience.19

Philip Morris International (PMI, New York, USA) launched the first iteration of the current generation of HTPs in 2014. It was developed as Tobacco Heating System (THS, version number 2.2), commercialised under the IQOS (PMI) brand name, and explicitly marketed to adult smokers unable to quit.20 As of September 2022, it was available in 68 countries. British American Tobacco (BAT, London, UK) launched glo in 2016 and Japan Tobacco (JTI, Tokyo, Japan) launched the HTP Ploom in the same year. Korean Tobacco and Ginseng (KT&G, Daejeon, South Korea) entered the HTP market with the launch of lil in 2017.


There are a myriad of systematic literature reviews and meta-analyses on the topics of smoking and COPD, with extensive high-level evidence supporting the causal relationship between the habit and disease.13,21-23 Although SFPs are increasingly used by adult smokers, there are fewer studies on the effects of HTPs compared to e-cigarettes. A simple query on PubMed for “e-cigarette” returns 5,495 results, versus 180 for “heated tobacco product.” Some groups have investigated health effects in smokers who switch to e-cigarettes.24,25 Fewer publications are related to HTPs. There is one systematic literature review on heat-not-burn tobacco products,26 and a Cochrane meta-analysis examined the use of HTPs for smoking cessation and reducing smoking prevalence.27 Almost no studies have assessed the individual and population health benefits from tobacco harm reduction for people with COPD and other chronic conditions who switch to SFPs instead of continuing to smoke. As more data are gathered, it is important to understand how alternatives like HTPs may reduce risk in patient populations.

This literature summary contains three sections. The first two describe the studies that support HTP harm reduction based on HPHC levels and a brief overview of pre-clinical findings. These publications are complemented by references to statements from regulatory bodies. The third section describes findings from the above-described literature search that identified published clinical data of HTP effects on HPHC exposure and smoking-related respiratory diseases. The narrative review concludes with a discussion of the cited studies, limitations of the data, and gaps in the literature to be addressed.

The goals of this narrative review were to provide a high-level summary of the studies performed to demonstrate that HPHC levels are lower in HTPs compared to cigarettes; and to identify studies on health outcomes in patients with COPD who switch from combustible cigarettes to HTPs. The publications were identified in the PubMed, Scopus, Embase, Google Scholar, and SciFinder databases using the following search string: (((chronic obstructive pulmonary syndrome[Title/Abstract]) OR (COPD[Title/Abstract])) AND (heated tobacco product[Title/Abstract])) OR (tobacco heating system[Title/Abstract]). The authors also searched the reference lists of relevant reviews and meta-analyses.


Harmful and Potentially Harmful Constituents Levels

The absence of combustion during THS use and the fact that THS aerosol is not smoke have been validated by leading scientific experts in the fields of combustion, fire safety, and thermochemistry from numerous countries, including Italy, the UK, Japan, Poland, the USA, Australia, Germany, and Switzerland, as well as by an independent research organisation in New Zealand.28

By avoiding combustion, THS generates an aerosol that contains significantly fewer harmful chemicals. Relative to smoke from a reference cigarette, the levels of International Agency Research on Cancer (IARC) Group 1 carcinogens in THS aerosol are reduced on average by >95%.29,30 Compared to cigarettes, THS also emits >94% lower levels of free radicals31 and 85% lower levels of reactive O2 species.32 A 2022 review concluded that SFPs, including e-cigarettes and HTPs, had a reduced effect on oxidative stress compared to cigarette smoking, with the caveat that more investigation is needed to clarify the long-term toxicological impact.33

The significant HPHC reduction in THS aerosol was confirmed by various public health authorities and independent laboratories around the world. In April 2019, the U.S. Food and Drug Administration (FDA) Center for Tobacco Products (CTP) issued a marketing order34 for PMI’s IQOS Tobacco Heating System to allow its introduction in the USA market. In its scientific review of the regulatory application,35 the FDA “found that the aerosol produced by the product under consideration ‘contains fewer toxic chemicals than cigarette smoke’, and many of the toxins identified are present at lower levels than in cigarette smoke. For example, the CO exposure [resulting from this product] is comparable to environmental exposure, and levels of acrolein and formaldehyde are 89–95% and 66–91% lower than from combustible cigarettes, respectively.” In July 2020, the FDA authorised the marketing of IQOS as a modified risk tobacco product with the following information: the IQOS system heats tobacco but does not burn it; this significantly reduces HPHC production; and scientific studies have shown that switching completely from conventional cigarettes to the IQOS system reduces user exposure to HPHCs.36

The German Federal Institute for Risk Assessment (BfR) also conducted an independent analysis of THS and found that the “levels of major carcinogens are markedly reduced in the emissions of the analysed [heat not burn] product in relation to the conventional tobacco cigarettes, and that monitoring these emissions using standardised machine smoking procedures generates reliable and reproducible data, which provide a useful basis to assess exposure and human health risks.”37

Published research on existing HTPs available in various markets confirms the reduction in the number and levels of HPHCs.38-42 This is in line with the statement from Public Health England (PHE, now under the UKHSA) that, “compared with cigarette smoke, heated tobacco products are likely to expose users and bystanders to lower levels of particulate matter, and harmful and potentially harmful compounds. The extent of the reduction found varies between studies.” In addition, “[t]he available evidence suggests that heated tobacco products may be considerably less harmful than tobacco cigarettes, and more harmful than e-cigarettes.”43 However, it is important to note that this potential HPHC reduction should be assessed on a product-by-product basis.

Pre-Clinical Findings

COPD is characterised by airway inflammation, damage, and remodelling.1,4 High levels of HPHCs in cigarette smoke irritate the lungs, introduce free radicals, and stimulate the production of proinflammatory chemokines and cytokines.10 Several in vivo studies have shown that the reduced exposure to HPHCs following THS use translates into lower levels of biomarkers of exposure and significantly reduced biological impacts on the rodent respiratory tract.44-47 These effects of lower exposure manifest as reduced disturbances in biological processes associated with COPD (including oxidative stress, inflammation, and apoptosis), less severe adaptive changes in respiratory tissues, absence of alveolar destruction (emphysema), and reduced pulmonary dysfunction.44,47 Emma et al.33 recently published a detailed review on how HTPs may also impact oxidative stress. They concluded that HTPs appear to have a better safety profile than cigarettes but suggested further long-term studies.33

While aerosols from HTPs appear to be less harmful than cigarette smoke, they may still induce changes. One group reported that HTP exposure induced apoptosis-mediated pulmonary emphysema in mouse lungs.48 Another recent study concluded that HTP aerosol altered rat ultrastructural lung airways and DNA.49 Gu et al.50 found that mice exposed to HTP aerosol exposure for 24 weeks had increased proinflammatory cytokine levels in the lung, impaired pulmonary function, and lung tissue damage. However, many of these changes were not as significant as those induced by cigarette smoke.48-50

Clinical Findings

Human clinical trials with THS indicate that reduced HPHC exposure may have a lower impact on smokers’ health compared to continued combustible cigarette use. However, most studies focused on measuring biomarkers of exposure to toxicants or potential harm as proxies to assess cardiovascular and respiratory disease, and cancer.51 Only a handful of publications have actually examined lung function in smokers. In a clinical trial in Japan, healthy smokers who were not willing to quit switched from menthol cigarettes to menthol THS for 5 days in confinement and 85 days in ambulatory settings, and showed improved lung function (i.e., higher FEV1), similar to that measured in subjects who stopped smoking.52 The authors proposed that this was due to decreased lung inflammation after switching from cigarettes. In a 6-month clinical study in the USA, smokers who switched from smoking cigarettes to predominant THS use showed significant improvements in clinical risk endpoints associated with O2 delivery (decreased carboxyhaemoglobin levels), inflammation (reduced white blood cell count), and COPD (increased FEV1), although their plasma nicotine levels remained similar to that in smokers.53

A longitudinal epidemiological study54 of a Kazakhstani population showed that adult smokers who switched to HTPs showed less decline in health-related parameters than subjects who continued to smoke combustible cigarettes after 1, 2, and 4 years of follow-up. Although the study did not specifically assess subjects with COPD, the cohort included individuals aged 40–59 years with a minimum 10 pack-year smoking history. Smokers who switched to HTPs had fewer respiratory symptoms, better lung function (forced vital capacity and FEV1) and physical exercise capacity (assessed with a 6 Minute Walk Test [6MWT]), and healthier metabolic syndrome parameters (waist circumference, high-density lipoprotein cholesterol levels, and systolic blood pressure) than cigarette smokers.55-57

One group specifically analysed data from a COPD cohort for 3 years after smokers with COPD switched to HTPs. Despite the small number of patients in their study (n=38), Polosa et al.58 found that patients with COPD using HTPs experienced fewer COPD exacerbations and significant improvements in symptoms, exercise capacity, and overall health-related quality of life than patients who continued to smoke cigarettes.58 Importantly, the authors performed a subgroup analysis of dual users who continued to smoke combustible cigarettes in addition to HTPs (n=8) and found a marked reduction in the number of cigarettes smoked per day (confirmed by exhaled CO measurement).58,59 A cross-sectional study from the same research group60 analysed mucociliary clearance, a known biomarker of early respiratory health changes, by measuring the saccharin transit time after SFP use. The median saccharin transit time was almost twice as long in cigarette smokers (13.15 min) compared to never (7.24 min) and former smokers who had abstained for at least 3–6 months (7.26 min). Subjects in the HTP study group had a saccharin transit time (8.00 min), similar to former and never smokers. Based on these findings, the authors concluded that switching from cigarettes to HTPs has a beneficial impact on mucociliary clearance, which could be considered an early respiratory health change.

After their introduction to Japan in 2014, the prevalence of HTP use increased 50-fold from 2015–2019, from 0.2% to 11.3%.61 This coincided with a rapid decrease in cigarette sales in the country, from 186.2 billion sticks in 2014 to 120.9 billion in 2019.62 A recent real-world evidence study analysed hospitalisation numbers associated with COPD using data from the Japanese Medical Data Center (JMDC) over this same time period.63 Careful evaluation of all available data from the JMDC database revealed a significant reduction in the number of hospitalisations for COPD and a non-significant reduction in hospitalisations for COPD plus lower respiratory tract infections after the 2014 THS introduction (Figure 2).

Figure 2: Chronic obstructive pulmonary disease hospitalisation rate over time in Japan (data acquired from the Japanese Medical Data Center [JMDC] database).
The increasing trend of COPD hospitalisations turned downward in 2017, shortly after the introduction of HTPs to Japan.
COPD: chronic obstructive pulmonary disease; HTP: heated tobacco product; JMDC: Japanese Medical Data Center.
Adapted from van der Plas et al.63


Although HTPs have only been marketed for a decade, there is a considerable body of evidence from industry and independent studies that HTPs generate lower levels of HPHCs. A Cochrane meta-analysis on 13 clinical studies involving HTPs concluded that there was moderate-certainty evidence that HTP users are exposed to lower levels of HPHCs than smokers.27 There are also numerous pre-clinical studies supporting their relative safety compared to cigarettes.44-50 However, the clinical picture is less clear. A systematic review on HTP exposure and adverse health effects found just 17 studies investigating the effects of HTPs on human health, most of which were short term.64 The authors’ review of the literature identified a small number of studies55-58 that longitudinally assessed lung function in middle-aged subjects who continued to smoke or switched to HTPs, but they were not specifically recruited from a patient population with COPD. In patient-focused studies, the actual numbers of subjects with lung disease or COPD were very low: n=51 (continued smoking) and n=25 (switched to HTPs) in Sharman et al.57 and n=19 in both arms of Polosa et al.58 Real-world evidence studies such as the publication by van der Plas et al.62 can provide some insight into how these products affect population health, but there are many limitations to this type of research. While the results highlight associations, they cannot be used to infer a causal relationship. Longer studies with different designs will ultimately determine whether these findings reflect a reduction in COPD morbidity.

This narrative review also highlights a significant literature gap regarding HTP use by patients with chronic conditions, including COPD. A recent survey on HTP use by subjects with chronic conditions only included 42 patients with COPD out of 9,008 respondents,64 and 33.3% were using HTPs in conjunction with conventional cigarettes. Clearly, more information is needed to determine if completely switching to HTPs improves the quality of life and health outcomes of patients with COPD who would otherwise continue to smoke. This will require multiple lines of evidence from surveys of patients with chronic conditions, continued surveillance of real-world evidence, and the completion of Phase IV trials that will take several years. As noted in a recent meta-analysis,26 only 11 randomised controlled trials have assessed HTP safety and the median follow-up was just 13 weeks. A clinical trial sponsored by PMI is currently recruiting subjects for a 3-year study to assess the effect of switching from cigarette smoking to THS on disease progression in subjects with mild to moderate COPD with chronic bronchitis;65 the estimated study completion date is June 2027.

It is worth noting that HTPs were only recently authorised for sale in the USA (in 2019) and they are currently only available in a few cities. Presumably, more researchers will study their effects as HTP uptake increases in the USA and around the globe.


The congruence of recent scientific findings indicates that adult smokers who completely switch to HTPs could have a lower risk of COPD development and progression than those who continue smoking. However, the paucity of studies on this specific topic limit the strength of this conclusion. Further epidemiological studies, additional follow-up of real-world data, and prospective clinical trials are needed to understand the impact of switching to HTPs on health outcomes in COPD.

In closing, it is important to state that HTPs are not risk-free and contain nicotine. Although nicotine is addictive, it is not the primary cause of smoking-related diseases.14 The best choice any smoker can make continues to be quitting cigarettes and nicotine altogether. If they choose to switch to HTPs, they should be informed that dual use with conventional cigarettes is not advised.

National Health Service (NHS). Chronic obstructive pulmonary disease (COPD). 2019. Available at: https://www.nhs.uk/conditions/chronic-obstructive-pulmonary-disease-copd/causes/. Last accessed: 19 December 2022. Salvi SS, Barnes PJ. Chronic obstructive pulmonary disease in non-smokers. Lancet. 2009;374(9691):733-43. World Health Organization (WHO). The top 10 causes of death - factsheet. 2018. Available at: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death. Last accessed: 19 December 2022. Centers for Disease Control and Prevention (CDC). Health effects of cigarette smoking. 2020. Available at: https://www.cdc.gov/tobacco/data_statistics/fact_sheets/health_effects/effects_cig_smoking/. Last accessed: 19 December 2022. Kamal R et al. Meta-analysis approach to study the prevalence of chronic obstructive pulmonary disease among current, former and non-smokers. Toxicol Rep. 2015;2:1064-74. Rezaei S et al. Economic burden of smoking: a systematic review of direct and indirect costs. Med J Islam Repub Iran. 2016;30:397. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the preven-tion, diagnosis and management of COPD: 2023 report. 2023. Available at: https://goldcopd.org/2023-gold-report-2/. Last accessed: 19 December 2022. Li X et al. Smoking status affects clinical characteristics and disease course of acute exacerbation of chronic obstructive pulmonary disease: a prospectively observational study. Chron Respir Dis. 2020;17:1479973120916184. Centers for Disease Control and Prevention (US); NCfCDPaHP, Office on Smoking and Health (US), Pulmonary diseases. How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease: a report of the surgeon general [Internet] (2010) Atlanta: Centers for Disease Control and Prevention (US). Available at: https://www.ncbi.nlm.nih.gov/books/NBK53017/. Last accessed: 19 December 2022. Vozoris NT, Stanbrook MB. Smoking prevalence, behaviours, and cessation among individuals with COPD or asthma. Respir Med. 2011;105(3):477-84. Schauer GL et al. Smoking prevalence and cessation characteristics among U.S. adults with and without COPD: findings from the 2011 Behavioral Risk Factor Surveillance System. COPD. 2014;11(6):697-704. Pashutina Y et al. Attempts to quit smoking, use of smoking cessation methods, and associated characteristics among COPD patients. NPJ Prim Care Respir Med. 2022;32(1):50. Hoogendoorn M et al. Long-term effectiveness and cost-effectiveness of smoking cessation interventions in patients with COPD. Thorax. 2010;65(8):711-8. Royal College of Physicians (RCP). Nicotine without smoke. Tobacco harm reduction. 2016. Available at: https://www.rcplondon.ac.uk/projects/outputs/nicotine-without-smoke-tobacco-harm-reduction. Last accessed: 19 December 2022. DiPiazza J et al. Sensory experiences and cues among E-cigarette users. Harm Reduct J. 2020;17(1):75. Palmer AM et al. Distinct influences of nicotine and sensorimotor stimuli on reducing cravings to smoke and vape among dual users. Addict Behav. 2021;122:107051. Tompkins CNE et al. Factors that influence smokers’ and ex-smokers’ use of IQOS: a qualitative study of IQOS users and ex-users in the UK. Tob Control. 2021;30(1):16-23. Cozzani V et al. An experimental investigation into the operation of an electrically heated tobacco system. Thermochim Acta. 2020;684:178475. Philip Morris International (PMI). Why combustion is the primary problem with cigarettes. 2022. Available at: https://www.pmiscience.com/en/smoke-free/combustion/. Last accessed: 22 February 2023. Philip Morris International (PMI). Heated tobacco products (HTPs). Information sheet. 2020. Available at: https://www.pmiscience.com/content/dam/pmiscience/en/pdfs/smoke-free-approach/heated-tobacco-products-htp-frequently-asked-questions-infosheet.pdf. Last accessed: 19 December 2022. Lee PN et al. The relationship of cigarette smoking in Japan to lung cancer, COPD, ischemic heart disease and stroke: a systematic review. F1000Res. 2018;7:204. Chen H et al. Epidemiological evidence relating risk factors to chronic obstructive pulmonary disease in China: a systematic review and meta-analysis. PLoS One. 2021;16(12):e0261692. Verma A et al. Prevalence of COPD among population above 30 years in India: a systematic review and meta-analysis. J Glob Health. 2021;11:04038. Bozier J et al. The evolving landscape of e-cigarettes: a systematic review of recent evidence. Chest. 2020;157(5):1362-90. Wills TA et al. E-cigarette use and respiratory disorders: an integrative review of converging evidence from epidemiological and laboratory studies. Eur Respir J. 2021;57(1):1901815. Simonavicus E et al. Heat-not-burn tobacco products: a systematic literature review. Tob Control. 2019;28(5):582-94. Tattan-Birch H et al. Heated tobacco products for smoking cessation and reducing smoking prevalence. Cochrane Database Syst Rev. 2022;1(1):CD013790. Nordlund M et al. Scientific substantiation of the absence of combustion in the electrically heated tobacco product (EHTP) and that the aerosol emitted is not smoke. 2020. Available at: https://www.pmiscience.com/en/research/publications-library/scientific-substantiation-of-the-absence-of-combustion-in-the-electrically-heated-tobacco-product-ehtp-and-that-the-aerosol-emitted-is-not-smoke/. Last accessed: 19 December 2022. Schaller J-P et al. Evaluation of the Tobacco Heating System 2.2. Part 3: influence of the tobacco blend on the formation of harmful and potentially harmful constituents of the Tobacco Heating System 2.2 aerosol. Regul Toxicol Pharmacol. 2016;81(2):S48-58. Schaller J-P et al. Evaluation of the Tobacco Heating System 2.2. Part 2: chemical composition, genotoxicity, cytotoxicity, and physical properties of the aerosol. Regul Toxicol Pharmacol. 2016;81(Suppl 2):S27-47. Shein M, Jeschke G. Comparison of free radical levels in the aerosol from conventional cigarettes, electronic cigarettes, and heat-not-burn tobacco products. Chem Res Toxicol. 2019;32(6):1289-98. Salman R et al. Free-base and total nicotine, reactive oxygen species, and carbonyl emissions from IQOS, a heated tobacco product. Nicotine Tob Res. 2019;21(9):1285-8. Emma R et al. The impact of tobacco cigarettes, vaping products and tobacco heating products on oxidative stress. Antioxidants (Basel). 2022;11(9):1829. U.S. Food and Drug Administration (FDA). FDA: IQOS marketing order, April 30, 2019. 2019. Available at: https://www.fda.gov/media/124248/download. Last accessed: 19 December 2022. U.S. Food and Drug Administration (FDA). Executive summary: technical project lead review (TPL) for PMTAs for IQOS. 2019. Available at: https://www.fda.gov/media/124247/download. Last accessed: 19 December 2022. U.S. Food and Drug Administration (FDA). Scientific review of modified risk tobacco product application (MRTPA) under section 911(d) of the FD&C Act -technical project lead. 2020. Available at: https://www.fda.gov/media/139796/download. Last accessed: 19 December 2022. Mallock N et al. Levels of selected analytes in the emissions of “heat not burn” tobacco products that are relevant to assess human health risks. Arch Toxicol. 2018;92(6):2145-9. Bekki K et al. Comparison of chemicals in mainstream smoke in heat-not-burn tobacco and combustion cigarettes. J UOEH. 2017;39(3):201-7. Uchiyama S et al. Simple determination of gaseous and particulate compounds generated from heated tobacco products. Chem Res Toxicol. 2018;31(7):585-93. Jaccard G et al. Comparative assessment of HPHC yields in the Tobacco Heating System THS2.2 and commercial cigarettes. Regul Toxicol Pharmacol. 2017;90:1-8. Li X et al. Chemical analysis and simulated pyrolysis of Tobacco Heating System 2.2 compared to conventional cigarettes. Nicotine Tob Res. 2018;21(1):111-8. Pieper E et al. Tabakerhitzer als neues produkt der tabakindustrie: gesundheitliche risiken. Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz. 2018;61(11):1422-8. Public Health of England (PHE). Evidence review of e-cigarettes and heated tobacco products 2018: executive summary. 2018. Available at: https://www.gov.uk/government/publications/e-cigarettes-and-heated-tobacco-products-evidence-review/evidence-review-of-e-cigarettes-and-heated-tobacco-products-2018-executive-summary. Last accessed: 19 December 2022. Phillips B et al. An 8-month systems toxicology inhalation/cessation study in Apoe-/- mice to in-vestigate cardiovascular and respiratory exposure effects of a candidate modified risk tobacco product, THS 2.2, compared with conventional cigarettes. Toxicol Sci. 2016;149(2):411-32. Wong ET et al. Evaluation of the Tobacco Heating System 2.2. Part 4: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects compared with cigarette smoke. Regul Toxicol Pharmacol. 2016;81(Suppl 2):S59-81. Oviedo A et al. Evaluation of the Tobacco Heating System 2.2. Part 6: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects of a mentholated version compared with mentholated and non-mentholated cigarette smoke. Regul Toxicol Pharmacol. 2016;81(Suppl 2):S93-122. Phillips B et al. A six-month systems toxicology inhalation/cessation study in ApoE−/− mice to investigate cardiovascular and respiratory exposure effects of modified risk tobacco products, CHTP 1.2 and THS 2.2, compared with conventional cigarettes. Food Chem Toxicol. 2019;126:113-41. Nitta NA et al. Exposure to the heated tobacco product IQOS generates apoptosis-mediated pulmonary emphysema in murine lungs. Am J Physiol Lung Cell Mol Physiol. 2022;322(5):L699-711. Vivarelli F et al. Unburned tobacco cigarette smoke alters rat ultrastructural lung airways and DNA. Nicotine Tob Res. 2021;23(12):2127-34. Gu J et al. Chronic exposure to IQOS results in impaired pulmonary function and lung tissue damage in mice. Toxicol Lett. 2023;374:1-10. Akiyama Y, Sherwood N. Systematic review of biomarker findings from clinical studies of electronic cigarettes and heated tobacco products. Toxicol Rep. 2021;8:282-94. Lüdicke F et al. Effects of switching to the menthol Tobacco Heating System 2.2, smoking abstinence, or continued cigarette smoking on clinically relevant risk markers: a randomized, controlled, open-label, multicenter study in sequential confinement and ambulatory settings (Part 2). Nicotine Tob Res. 2018;20(2):173-82. Lüdicke F et al. Effects of switching to a heat-not-burn tobacco product on biologically relevant biomarkers to assess a candidate modified risk tobacco product: a randomized trial. Cancer Epidemiol Biomarkers Prev. 2019;28(11):1934-43. Sharman A et al. Lung function in users of a smoke-free electronic device with HeatSticks (iQOS) versus smokers of conventional cigarettes: protocol for a longitudinal cohort observational study. JMIR Res Protoc. 2018;7(11):e10006. Sharman A, Nurmagambetov T. Changes in respiratory function and physical capacity among smokers after switching to IQOS: one year follow-up. Global J Respir Care. 2020;6:22-9. Sharman A et al. Respiratory function and physical capacity in combustible cigarettes and heated tobacco products users: a two-year follow-up cohort study. Global J Respir Care. 2021;7:27-34. Sharman A et al. Respiratory function, physical capacity, and metabolic syndrome components in combustible cigarettes and heated tobacco products users: a four-year follow-up cohort study. Global J Respir Care. 2022;8:4-10. Polosa R et al. Health outcomes in COPD smokers using heated tobacco products: a 3-year follow-up. Intern Emerg Med. 2021;16(3):687-96. Tashkin DP. Smoking cessation in COPD: confronting the challenge. Intern Emerg Med. 2021;16(3):545-7. Polosa R et al. Impact of exclusive e-cigarettes and heated tobacco products use on muco-ciliary clearance. Ther Adv Chronic Dis. 2021;12:20406223211035267. Odani S, Tabuchi T. Prevalence of heated tobacco product use in Japan: the 2020 JASTIS study. Tob Control. 2022;31(e1):e64-5. Cummings KM et al. What is accounting for the rapid decline in cigarette sales in Japan? Int J Environ Res Public Health. 2020;17(10):3570. van der Plas A et al. Ischemic heart disease and chronic obstructive pulmonary disease hospitalizations in Japan before and after the introduction of a heated tobacco product. Front Public Health. 2022;10:909459. Znyk M et al. Exposure to heated tobacco products and adverse health effects, a systematic review. Int J Environ Res Public Health. 2021;18(12):6651. Nakama C, Tabuchi T. Use of heated tobacco products by people with chronic diseases: the 2019 JASTIS study. PLoS One. 2021;16(11):e0260154. Philip Morris Products S.A.. Effect of switching from cigarette smoking to THS on disease progression in mild to moderate COPD subjects with chronic bronchitis symptoms. NCT05569005. https://clinicaltrials.gov/show/NCT05569005.

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